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The synthesis of the 2 H, 3 H, and 14 C‐isotopomers of 2′‐deoxy‐2′,2′‐difluorocytidine hydrochloride, an anti‐tumor compound
Author(s) -
Wheeler William J.,
Mabry Thomas E.,
Jones C. David
Publication year - 1991
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580290510
Subject(s) - chemistry , isotopomers , hydrogenolysis , hydrochloride , deuterium , tritium , chemical synthesis , ammonia , medicinal chemistry , stereochemistry , organic chemistry , catalysis , biochemistry , physics , quantum mechanics , molecule , nuclear physics , in vitro
The 2 H, 3 H, and 14 C‐isotopomers of 2′‐deoxy‐2′,2′‐difluorocytidine hydrochloride ( 1a , gemcitabine hydrochloride) have been synthesized in two radiochemical steps from the reaction of bis ‐trimethylsilylcytosine‐[2‐ 14 C] and 3,5‐O‐ bis ‐benzoyl‐1‐O‐methanesulfonyl‐2‐ deoxy‐2,2‐difluororibose ( 2b ). A mixture of anomers of 3′,5′‐dibenzoyl‐2′‐deoxy‐2′,2′‐difluorocytidine ( 4a ) or its 14 C‐isotopomer ( 4b ) were obtained which were readily separated by crystallization from ethyl acetate. Deprotection using methanolic ammonia yielded the target compound. The 2 H and 3 H‐isotopomers were prepared by deuterium (or tritium) gas hydrogenolysis of 5‐iodo‐2′‐deoxy‐2′,2′‐difluorocytidine ( 5 ).